The neurobiological basis of social dysfunction and the high male prevalence in autism spectrum disorder (ASD) remain poorly understood. Although network alterations presumably underlie the development of autistic-like behaviors, a clear pattern of connectivity differences specific to ASD has not yet emerged. Because the heterogeneous nature of ASD hinders investigations in human subjects, we explored brain connectivity in an etiologically homogenous rat model of ASD induced by exposure to valproic acid (VPA) in utero. We performed partial correlation analysis of cross-sectional resting-state 18F-fluorodeoxyglucose positron emission tomography scans from VPA-exposed and control rats to estimate metabolic connectivity and conducted canonical correlation analysis of metabolic activity and behavior scores. VPA-treated rats exhibited impairments in social behaviors, and this difference was more pronounced in male than female rats. Similarly, current analyses revealed sex-specific changes in network connectivity and identified distinct alterations in the distributed metabolic activity patterns associated with autistic-like social deficits. Specifically, diminished activity in the salience network and enhanced activity in a cortico-cerebellar circuit correlated with the severity of social behavioral deficits. Such metabolic connectivity features may represent neurobiological substrates of autistic-like behavior, particularly in males, and may serve as a pathognomonic sign in the VPA rat model of ASD.

Individuality, the uniqueness that distinguishes one person from another, may manifest as diverse rearrangements of functional connectivity during heterogeneous cognitive demands; yet, the neurobiological substrates of individuality, reflected in inter-individual variations of large-scale functional connectivity, have not been fully evidenced. Accordingly, we explored inter-individual variations of functional connectivity dynamics, subnetwork patterns and modular architecture while subjects watched identical video clips designed to induce different arousal levels. How inter-individual variations are manifested in the functional brain networks was examined with respect to four contrasting divisions: edges within the anterior versus posterior part of the brain, edges with versus without corresponding anatomically-defined structural pathways, inter- versus intra-module connections, and rich club edge types. Inter-subject variation in dynamic functional connectivity occurred to a greater degree within edges localized to anterior rather than posterior brain regions, without adhering to structural connectivity, between modules as opposed to within modules, and in weak-tie local edges rather than strong-tie rich-club edges. Arousal level significantly modulates inter-subject variability in functional connectivity, edge patterns, and modularity, and particularly enhances the synchrony of rich-club edges. These results imply that individuality resides in the dynamic reconfiguration of large-scale brain networks in response to a stream of cognitive demands.

The heterogeneous presentation of inattentive and hyperactive-impulsive core symptoms in attention deficit hyperactivity disorder (ADHD) warrants further investigation into brain network connectivity as a basis for subtype divisions in this prevalent disorder. With diffusion and resting-state functional magnetic resonance imaging data from the Healthy Brain Network database, we analyzed both structural and functional network efficiency and structure-functional network (SC-FC) coupling at the default mode (DMN), executive control (ECN), and salience (SAN) intrinsic networks in 201 children diagnosed with the inattentive subtype (ADHD-I), the combined subtype (ADHD-C), and typically developing children (TDC) to characterize ADHD symptoms relative to TDC and to test differences between ADHD subtypes. Relative to TDC, children with ADHD had lower structural connectivity and network efficiency in the DMN, without significant group differences in functional networks. Children with ADHD-C had higher SC-FC coupling, a finding consistent with diminished cognitive flexibility, for all subnetworks compared to TDC. The ADHD-C group also demonstrated increased SC-FC coupling in the DMN compared to the ADHD-I group. The correlation between SC-FC coupling and hyperactivity scores was negative in the ADHD-I, but not in the ADHD-C group. The current study suggests that ADHD-C and ADHD-I may differ with respect to their underlying neuronal connectivity and that the added dimensionality of hyperactivity may not explain this distinction.